JungmannLab

doi.orgMolecular mapping in DNA-PAINT via modified Gaussian Mixture Modeling - Nature CommunicationsStandard algorithms fail to fully exploit the spatial information in DNA-PAINT. Here, the authors present G5M, an algorithm providing molecular maps by accurately inferring biomolecule positions at di...

In DNA-PAINT, nearby proteins create overlapping localizations. You may see two by eye, but analysis often misses them, wasting precious precision. G5M solves this. Now in @natcomms.nature.com. doi.org/10.1038/s414.... 1/7

github.comGitHub - jungmannlab/picasso: A collection of tools for painting super-resolution imagesA collection of tools for painting super-resolution images - jungmannlab/picasso

G5M is implemented in Picasso since version 0.9.5: github.com/jungmannlab/..., although we always recommend using the most recent version! A short documentation: picassosr.readthedocs.io/en/latest/re.... We advise reading the whole paper for best results! 6/7

We hope G5M pushes molecular mapping forward. Excited to see the discoveries it enables! Thanks to @rafalkowalew.bsky.social, @susannereinhardt.bsky.social, @ipachmayr.bsky.social, Shuhan Xu, @lumasullo.bsky.social for developing G5M and the @jungmannlab.bsky.social for testing and improving it. 7/7

We validated G5M on DNA origami, Nuclear Pore Complexes (NPCs) and Obinutuzumab-treated CD20 RESI data. In NPCs, G5M found twice as many Nup96 dimers as GA, demonstrating increased accuracy in molecular mapping. 4/7

Bonus: we found a new formula for axial loc. precision for astigmatic imaging for any z position. It only depends on the 3D calibration and the properties of localizations. Interestingly, the results are not necessarily symmetric around z = 0. 5/7

Knowing where biomolecules are is key to uncovering molecular interactions and patterns. But standard clustering methods (e.g., DBSCAN, GA) often fail when proteins are spaced <5× the localization precision, leading to false negatives and misassignments. 2/7

G5M uses modified Gaussian mixture modeling to accurately capture the shape of 2D and 3D astigmatic localization clouds. In realistic simulations, it resolves molecules spaced 2.9 localization precisions apart with a 27× higher recovery rate than other tools. 3/7

onlinelibrary.wiley.comDynamic Binder Exchange Improves Protein Labeling Efficiency in DNA‐PAINT up to 15‐FoldDynamic Binder Exchange (DyBE) leverages transient binder–target interactions to enhance labeling efficiency by up to 15-fold in super-resolution microscopy. DyBE maps nanoscale receptor tyrosine kin...

Up to 15-fold improvement in protein labeling for DNA-PAINT 🧬🔬. We are excited to present our latest work published in @angewandtechemie.bsky.social! onlinelibrary.wiley.com/doi/10.1002/...

Importantly, this workflow is broadly applicable and compatible with virtually any high off-rate binder. Many “bad” binders currently sitting in lab freezers may now become powerful imaging tools. 5/6

Big congrats to Clemens Steinek, @ipachmayr.bsky.social, and Sebastian Strauss who led the project as well as other co-authors that contributed to this work!! 6/6

Up to 15-fold improvement in protein labeling for DNA-PAINT 🧬🔬. We are excited to present our latest work published in @angewandtechemie.bsky.social! onlinelibrary.wiley.com/doi/10.1002/...

DyBE increases protein labeling up to 15-fold for high off-rate nanobodies, enabling visualization of most molecules of a given target protein within the cell. 3/6

Using DyBE, we resolved the organization of receptor tyrosine kinases at single-protein resolution and detected ligand-dependent homodimerization of HER2, as well as EGF-induced formation of EGFR homodimers and EGFR–HER2 heterodimers. 4/6

Up to 15-fold improvement in protein labeling for DNA-PAINT 🧬🔬. We are excited to present our latest work published in @angewandtechemie.bsky.social! onlinelibrary.wiley.com/doi/10.1002/...

Here we introduce Dynamic Binder Exchange (DyBE), a new strategy that uses the high off-rate kinetics of small binders to map proteins with nanometer-scale precision! 1/6

@philippsteen.bsky.social

In classical DNA-PAINT, small binders such as nanobodies can localize proteins with nanometer precision, but rapid unbinding often limits efficient protein labeling. DyBE adapts DNA-PAINT to harness small, high off-rate binders for nanometer-precise sampling. 2/6

JungmannLab reposted

Philipp Steen

26 Jan

How do you scale super-resolution microscopy to dozens of proteins without linearly scaling imaging time? We introduce Combi-PAINT: a combinatorial DNA-PAINT strategy that breaks the 1-target-per-round bottleneck of Exchange-PAINT: www.biorxiv.org/content/10.6... 1/5

biorxiv.orgbiorxiv.org

JungmannLab reposted

SPIE

@spie.org

18 Jan

Ralf Jungmann, of the @mpibiochem.bsky.social, is the first speaker to step to the BiOS Hot Topics stage at #PhotonicsWest!💡 He is delivering his presentation titled: “From DNA nanotechnology to biomedical insight: towards single-molecule spatial omics” @jungmannlab.bsky.social

JungmannLab reposted

Nature Nanotechnology

@natnano.nature.com

17 Oct 2025

Now online: October 2025 Issue. - Focus Issue on #biosensing, - DNA moiré superlattices, - Sugars at Ångström-resolution, - Solid-state #nanopores, - Non-aqueous Li #batteries, - - Neuromorphic vision, - Peptide #hydrogels, - Deep learning for #LNPs and more... www.nature.com/nnano/volume...

Highly efficient 12-color multiplexing with speed-optimized DNA-PAINT. We are excited to share our latest paper in @natcomms.nature.com, using left-handed DNA to extend speed-optimized DNA-PAINT to 12 targets in a simple and straightforward way! 🧬👈🚀https://www.nature.com/articles/s41467-025-64228-x

Within this neuronal atlas we can reveal the three synapse classes, excitatory, inhibitory and the recently discovered mixed synapse. Organelle imaging of Peroxisomes (Pmp70) and the Golgi Apparatus (Golga5) reveals rare contact sides and even fused particles. (5/6)

Thanks to all who made this possible! @eduardunterauer.bsky.social @evaschentarra.bsky.social @ipachmayr.bsky.social @taishatashrin.bsky.social Jisoo Kwon Sebastian Strauss, @jekristina.bsky.social @rafalkowalew.bsky.social @opazo.bsky.social @forna.bsky.social @lumasullo.bsky.social (6/6)

We demonstrate speed-optimized left-handed DNA-PAINT by characterizing the sequence binding kinetics and resolving three main microscopy benchmarking targets, mitochondria, microtubules and nuclear pore complexes with <5 nm localization precision. (3/6)

To show the power of the technique, we acquired a 13-plex 200 x 200 µm2 neuronal atlas in 3D. With this atlas we map the interaction architecture of three neurons, resolving organelles, cytoskeleton, vesicles and synapses at single-protein resolution. (4/6)

@heilemannlab.bsky.social

The mirrored design of left-handed oligonucleotides allows the extension of the common 6 speed-sequences R1-R6 with their analogs L1-L6, enabling 12 target multiplexing with a standard secondary label-free DNA-PAINT workflow. (2/6)

JungmannLab reposted

Heilemann Lab

27 Aug 2025

Next on stage is Eduard Unterauer @eduardunterauer.bsky.social from @jungmannlab.bsky.social reporting spatial proteomics with DNA PAINT #SMLMS2025

nature.comÅngström-resolution imaging of cell-surface glycans - Nature NanotechnologyBy combining bioorthogonal metabolic labelling and resolution enhancement through sequential imaging of DNA barcodes, the molecular organization of individual sugars in the native glycocalyx has been ...

30 July 2025

We're excited that the study is now out in Nature Nanotechnology @natnano.nature.com www.nature.com/articles/s41...

Luciano A. Masullo@lumasullo.bsky.social

ÅNGSTRÖM-RESOLUTION IMAGING OF CELL-SURFACE GLYCANS 🧬🎨🍬 The glycocalyx, our cells' sugar coat, holds secrets in immunology, cancer, viral infections, and more. Visualizing its molecular architecture was impossible… until now. #glycotime #microscopy www.biorxiv.org/content/10.1...

JungmannLab reposted

Nature Nanotechnology

@natnano.nature.com

New paper online: Ångström-resolution imaging of cell-surface glycans. The molecular organization of sugars in the native #glycocalyx has been resolved at 9 ångström using bioorthogonal metabolic labeling and #superresolution imaging of DNA barcodes. #Glycotime www.nature.com/articles/s41...

Ever wondered what happens when therapeutic antibodies bind to cancer cells? In our latest study, we used multiplexed 3D-RESI to directly visualize how anti-CD20 antibodies interact with their receptors, revealing their precise arrangement at single-protein resolution. (1/6)

The shift from Type II to Type I function reveals a structure–function continuum for anti-CD20 antibodies, showing that receptor arrangements dictate mechanism of action. RESI provides a platform for structure-guided antibody development, applicable far beyond CD20. (5/6)

nature.comResolving the structural basis of therapeutic antibody function in cancer immunotherapy with RESI - Nature CommunicationsThe nanoscale organization of the antigen-antibody complexes influences the therapeutic action of monoclonal antibodies. Here, the authors present a multi-target 3D RESI imaging assay for the nanomete...

Congratulations to everyone involved: @ipachmayr.bsky.social, @lumasullo.bsky.social, @susannereinhardt.bsky.social, Jisoo Kwon, Ondřej Skořepa, Maite Llop, Sylvia Herter, Marina Bacac and Christian Klein. (6/6) Read the full story here: www.nature.com/articles/s41...

In contrast, Type II antibodies like Obinutuzumab and H299 induced limited oligomerization to dimers, trimers and tetramers, consistent with their role in promoting direct tumor cell death rather than complement activation. (3/6)

We showed a direct link between CD20 oligomerization and function by investigating OBZ-based T-cell engagers (TCEs). An increased IgG flexibility in the 2+1 TCE format lead to increased CD20 tetramerization, without higher-order clustering, resulting in a reduction of direct cytotoxicity. (4/6)

Max Planck Institute of Biochemistry

By imaging intact cells, we could see these therapeutic antibodies in action: Type I antibodies like Rituximab and Ofatumumab formed extended chains of CD20 hexamers or larger, creating platforms compatible with complement protein binding, mediating cancer cell killing. (2/6)

JungmannLab reposted

@mpibiochem.bsky.social

3 July 2025

Congratulations to Ralf on your election as a new EMBO member: ❕Original press release from @embo.org : www.embo.org/press-releas...

14 June 2025

Great science, great company and stunning views at our Lab retreat on Schloss Ringberg 🏰🧬🔬. Big thanks to our guests Sabrina Simoncelli, Sebastian Kobold, Thomas Schlichthärle, @massivephotonics.bsky.social & students from the @lfmilles.bsky.social and @mlsb-borgwardt.bsky.social Labs for joining!

nature.comSpatial and stoichiometric in situ analysis of biomolecular oligomerization at single-protein resolution - Nature CommunicationsExtracting quantitative information on biomolecular oligomerisation with high resolution remains a significant challenge. Here, the authors propose SPINNA, a framework that compares nearest-neighbour ...

Spatial and stoichiometric in situ analysis of biomolecular oligomerization at single-protein resolution We are excited to present our latest work published in @natcomms.nature.com www.nature.com/articles/s41...

@moniquehonsa.bsky.social , @philippsteen.bsky.social , Larissa Heinze, Shuhan Xu, Heinrich Grabmayr, Isabelle Pachmayr, Susanne C. M. Reinhardt, Ana Perovic, Jisoo Kwon, Ethan P. Oxley, Ross A. Dickins, Maartje M. C. Bastings, Ian A. Parish

@larissaheinze.bsky.social

To facilitate SPINNA’s widespread use in the scientific community, we offer an open-source Python implementation and a GUI available in the latest version of Picasso (github.com/jungmannlab/..., picassosr.readthedocs.io/en/latest/sp...). 7/7

Big congrats to @lumasullo.bsky.social and @rafalkowalew.bsky.social who led the project as well as other co-authors that contributed to this work!!

We further quantitatively evaluate the oligomerization of the Epidermal Growth Factor Receptor (EGFR) upon binding of its ligand, EGF. 5/7

Finally, we investigate the dimerization of CD80 and PD-L1, key surface ligands involved in immune cell signaling. 6/7

Here, we present SPINNA (Single-Protein Investigation via Nearest Neighbor Analysis): an analysis framework that compares nearest neighbor distances from experimental single-protein data with those from realistic simulations based on a user-defined model of protein oligomerization states. 3/7

We demonstrate SPINNA in DNA-origami, showing that it can infer not only the stoichiometry of the oligomers but also different spatial conformations. 4/7

Understanding how proteins assemble into complexes (oligomerize) within their native cellular environments is crucial for deciphering cellular signaling pathways 1/7